Prostate cancer is the most common cancer diagnosed in the United States and accounts for about 30% of cancer incidence. Etiology of prostate cancer is unknown, although familial factors, hormones, and dietary factors may play a role in the development of the disease. There is evidence that early onset prostate cancer may be attributed to an autosomal dominant germline mutation. It is estimated that one person in 170 may carry high risk alleles of the prostate cancer gene and that carriers of this gene have a lifetime risk of disease of 88% and non- carriers a lifetime risk of 5%. It is, therefore, very important to identify the gene, understand how it functions and identify what other exposures (genetic and/or environmental) interact with this gene. To our knowledge, there are to date non population-based studies that integrate (a) inherited susceptibility genes, (b) genetic alterations in selected oncogenes and tumor suppressor genes, and (c) environmental exposures. Using procedures we have developed in several on-going NCI funded genetic epidemiology studies, we propose to: (1) develop a population-based prostate cancer family registry of 524 families of probands under age 70. We will collect information on family history of cancer, dietary history, epidemiologic risk factors, and blood samples, from all probands, other prostate cancer affected relatives, and informative unaffected relatives. Tumor tissue samples will be collected from all cancer affected relatives; (2) characterize alterations on chromosome 1q in prostate cancer. Other potential loci associated with prostate cancer susceptibility will be considered for study as they become known. In the event that the prostate cancer susceptibility gene is cloned during the course of this study, we will test for mutations in the gene in order to estimate in the population frequency and penetrance; (3) assess whether expression of susceptibility genes (or presence of other genetic alterations) may be modified by environmental or host factors; (4) provide a well-characterized cohort of brothers/male cousins for the chemoprevention trial (Project III) and surrogate endpoint biomarker studies (Project II) of our Prostate Cancer Program Project. Data generated though this project will provide the basis on which high risk men for prostate cancer can be identified and programs on prevention and early detection can be developed.